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G N Wade

Publications and source records attributed to G N Wade.

At least 109 records · Page 6Linked to original sources
PubMed1980

Cytoplasmic estrogen, but not progestin, binding sites in male rat adipose tissues.

Male rat adipose tissues contain cytoplasmic estrogen binding sites comparable to those found in females. This bindng is of high affinity (Kd = 1.7 x 10(-10) M) and is estrogen specific. Binding of 17 beta-estradiol was inhibited by radioinert estrogens (17 beta-estradiol and R 2858) but not by other steroids (progesterone, 5 alpha-dihydrotestosterone, and corticosterone). Estrogen binding sites were found in all fat pads studied, but levels were highest in the epididymal pads. Treatment of female rats with 17 beta-estradiol benzoate (E2B) induced cytoplasmic progestin receptors in adipose tissues, but in three separate experiments, E2B treatment (20 microgram/day for 3 days) failed to induce measurable progestin ([3H]R 5020) binding sites in males. E2B treatment reduced lipoprotein lipase (LPL) activity by approximately 75% in epididymal (male) and parametrial (female) fat pads. Concurrent progesterone treatment increased parametrial LPL activity in E2B-treated females, but progesterone had no effect on epididymal fat pad LPL activity in males. These findings are consistent with the hypothesis that in male rats aromatized (estrogenic) metabolites of testosterone may reduce body fat content and alter lipid metabolism by direct actions on adipose tissues.

Adipose Tissue↗
PubMed1979

Insulin withdrawal impairs sexual receptivity and retention of brain cell nuclear estrogen receptors in diabetic rats.

Acute withdrawal of exogenous insulin significantly impairs estradiol and progesterone-induced sexual receptivity and retention of brain cell nuclear estrogen receptors in ovariectomized (OVX), streptozotocin-diabetic rats. Insulin withdrawal for 18--24 h of a 24 h estradiol benzoate (EB)-conditioning period resulted in significant reductions in mean lordosis ratings. Omission of insulin for any 12 h period during EB conditioning was without effect on sexual receptivity. 24 h insulin deprivation resulted in a signficant reduction of cell nuclear estrogen receptor levels in hypothalamus-preoptic area of rats sacrificed 26 h after EB administration. Withdrawal of insulin during the middle 12 h of conditioning had no significant effect on the quantities of brain cell nuclear estrogen receptors. These results are in agreement with the hypothesis that decreased cell nuclear binding of estradiol by neural target tissues may contribute to the reproductive dysfunctions of diabetics.

Animals↗
PubMed1979

Inhibition of estrous behavior by progesterone in rats: role of neural estrogen and progestin receptors.

Sexual receptivity can be induced in ovariectomized rats with sequential injections of 17 beta-estradiol-3-benzoate (EB; 2 micrograms sc) and progesterone given 24 h apart. If a high dose of progesterone is used, estrous behavior is followed by a period during which sexual receptivity cannot be reinduced with a second progesterone injection (sequential inhibition). We have examined the effects of a hormone treatment which causes a sequential inhibition on levels of estrogen and progestin receptors in the hypothalamus-preoptic area-septum of ovariectomized rats. In a preliminary experiment, a single injection of 2 micrograms EB caused a significant increase in the concentration of brain cell nuclear estrogen receptors, Peak levels were seen at 12-24 h and remained significantly elevated as long as 72 h after EB. In a second experiment, we found that 48 h after EB, brain cytoplasmic estrogen receptors were significantly depressed and nuclear estrogen receptors were significantly elevated. However, a single progesterone injection (5 mg, sc) 24 h after EB had no significant effect on either cytoplasmic or nuclear estrogen receptor levels. Forty-eight hours after EB, brain cytoplasmic progestin receptors were significantly elevated compared with oil-injected controls. In a third experiment, progesterone (5 mg, sc) given 24 h after EB reduced neural cytoplasmic progestin receptors to levels significantly below those of oil-injected controls at 48 h. These results are consistent with the suggestion that progesterone does not interact with neural estrogen receptors to inhibit lordosis in rats. Rather, we suggest that progesterone may induce a behavioral refractoriness to subsequent progesterone treatments, at least in part, by reducing the concentration of neural cytoplasmic progestin receptors.

Animals↗
PubMed1978

Cytoplasmic 17 beta-[3H]estradiol binding in rat adipose tissues.

Ovarian hormones, particularly 17 beta-estradiol, have important effects on body fat levels in rats, but it is not known whether 17 beta-estradiol can act directly on various fat depots to affect adiposity or whether these effects are entirely indirect (e.g. via food intake, exercise, or various metabolic actions). We have found high affinity, estrogen-specific macromolecular binding of 17 beta-[3H]estradiol in the cytoplasmic fraction of adipose tissues from ovariectomized rats. Saturation analysis indicates a Kd of 7.4 X 10(-10) M, and binding is inhibited by unlabeled 17 beta-estradiol or 11 beta-methoxy-17-ethynyl-1,3,5(10)-triene-3,17beta-diol (R2858) but not by progesterone, 5 alpha-dihydrotestosterone, or cortisol. 17 beta-[3H]Estradiol binding is virtually abolished by incubation with pronase but not with DNase or RNase, indicating that the binding macromolecule is probably a protein. Binding is seen in all adipose tissues studied, including abdominal, sc, and brown fat. Binding site concentration is highest in parametrial fat pads, followed by retroperitoneal, brown, omental, and inguinal depots. Binding is also seen in the cytoplasmic fraction of isolated parametrial adipocytes. These data indicate that the various adipose tissues might be estrogen target tissues in rats. Therefore, it is possible that estrogenic effects on body weight and composition could be mediated in part by direct estrogen action on adipose tissues.

Adipose Tissue↗
PubMed1977

Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes.

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.

Animals↗
PubMed1977

Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens.

The antiestrogens MER-25, CI-628, and nafoxidine inhibit the uptake of [3H]-estradiol in whole homogenates and isolated cell nuclei tissues and the pituitary, and inhibit estradiol-induced female sexual behavior. The antiestrogens were injected intraperitoneally 2 h prior to an intravenous injection of [3H]estradiol, and the animals were killed 2 h after the estradiol. CI-628 reduces radioactivity in whole homogenates and isolated cell nuclei of cerebral cortex, hypothalamus, preoptic area -septum and pituitary. Nafoxidine reduces uptake in cell nuclei of the hypothalamus, preoptic area-septum and pituitary. In this paradigm, MER-25 inhibited uptake only in the pituitary. In the analogous behavioral experiments, with antiestrogens injected 2 h prior to an intravenous injection of unesterified estradiol, CI-628 and nafoxidine totally inhibited lordosis responding. MER-25 shows no inhibition of behavior in this paradigm. However, when MER-25 is injected 12 h prior to the estradiol, it inhibits retention of [3H]estradiol at 2 h in brain and pituitary cell nuclei, and lordosis responding is also inhibited. Additionally, the antiestrogens can apparently displace previously bound [3H]estrdiol. When the antiestrogens are injected 2 h prior to an injection of [3H]estradiol, MER-25, CI-628 and nafoxidine all show greater inhibition of nuclear estradiol retention at 12 h after the [3H]estradiol injection than 2 h. Analogously, when CI-628 is injected 2 h after an intravenous injection of [3H]estradiol, it displaces most of the radioactivity present in hypothalamic-preoptic area nuclei at 12 h after the estradiol injection. These results indicate that antiestrogens can prevent or reverse the nuclear concentration of estradiol in brain cells and are consistent with a role of the cell nucleus in the induction of estrous behavior by estradiol.

Animals↗